This is a competing renewal K24 application for Viola Vaccarino, MD, PhD. The primary objective is to continue and expand an already successful research and mentoring program in patient-oriented research in the area of behavioral cardiology and mind-body relationships in cardiovascular disease (CVD). The success of this program was due in large part to the previous K24 support. The applicant was able to assemble substantial funding and collaboration opportunities, and attract many junior investigators who have worked productively under her mentorship; several have established an independent academic career. In order continue and build upon this work the PI seeks five additional years of protected time. The applicant's research involves the study of social, behavioral, and psychological determinants of cardiovascular risk, and the underlying mechanisms linking these factors to CVD. Her recent investigations supported by the K24 have produced significant contributions on the role of depression on the outcome of men and women with CVD, the role of inflammation, metabolic syndrome and autonomic function as they relate to depression, and role of genetic influences. Her most recent work has pioneered the concept of a central role played by genetic background in the relationship between depression and CVD or CVD risk factors. The applicant needs protected time to continue this pi^omising area of investigation and obtain new research grants. A main objective of the Pi's career development is maintaining and strengthening her mentoring program. The path to become a successful academic investigator is difficult and insecure. Patient-oriented researchers, especially those with clinical responsibilities, face special challenge. A critical goal ofthe Pi's program is to facilitate the route to academic advancement for promising new patient-oriented investigators. The applicant has become an essential member of many training programs at Emory and is a highly sought- after mentor. She seeks to secure protected time for the next five years so that she can continue her mentoring activities and expand them to attract a larger number of beginning investigators. Ultimately, Dr. Vaccarino's career goal is to contribute significantly to the advancement of the science and the clinical applications in the area of bio-behavioral relationships in CVD, through outstanding research and the training ofthe next generation of investigators.